A new catalytic mode of the modularly designed organocatalysts (MDOs): enantioselective synthesis of dihydropyrano[2,3-c]pyrazoles

The enantioselective tandem Michael addition-cyclization reaction between 3-methyl-2-pyrazolin-5-one and benzylidenemalononitriles was studied with modularly designed organocatalysts (MDOs) to yield 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles in high yields and moderate to good enantioselectivities. Most importantly, a new catalytic mode of the MDOs was established. Instead of being used as a nucleophile to form an enamine intermediate, the reaction center modules (amino acids) of the MDOs are now used as a Lewis base in this base-catalyzed reaction. Since there are more reactions catalyzed by Lewis bases than by the enamine mechanism, this finding greatly expands the scope of the MDOs in organic reactions. On the other hand, because the stereocontrolling modules (cinchona alkaloid derivatives) themselves may be used as Lewis base catalysts, this new method may also be viewed as an expeditious way for the modification of the reaction center of the cinchona alkaloid catalysts. (C) 2011 Elsevier Ltd. All rights reserved.